Question

For the regulation of the glycolysis pathways, what the molecules involved are and how they act.

Answer 1

The four regulatory enzymes are Hexokinase (or glucokinase in the liver), phosphofructokinase, and pyruvate kinase. And the regulation is also controlled by hormones Insulin and Glycogen.The major regulation step is regulation by phosphofructokinase (PFK).

Regulation by phosphofructokinase:

• Fructose-6-phosphate is converted to Fructose-1,6-biphosphate with the help of PFK. it is allosterically inhibited by ATP, but the inhibition is reversed by AMP. So, this allows glycolysis to be responsive to the energy needs of the cells, speeding up when ATP is in short supply. And slowing down when sufficient ATP is available.
• PFK is also inhibited by citrate, first product of citric acid cycle. The high level of citrate signals that there is a plentiful supply of citric acid cycle intermediate and hence no additional breakdown of glucose is required.   
• Fructose-6-phosphate stimulates the synthesis of Fructose-2,6-bisphosphate which in turn strongly activates PFK and hence activate the glycolysis pathway.

Regulation by Hormones:

• When blood glucose level falls, Glucagon is released and it triggers a C-AMP cascade that leads to the Phosphorylation of PFK2 and FBPase 2(Fructose 1,6-bisphosphatase) by Protein kinase A. This will activate FBPase and inhibit PFK2, lowering the level of Fructose-2,6-bisphosphate and decreasing the rate of glycolysis
• When glucose level is rise, the phosphate group is removed from PFK2 and FBPase2 by a phosphatase enzyme and thus inhibiting FBPase2 and activating PFK2, which rises the level of Fructose-2,6-bisphosphate and hence increase the rate of glycolysis

Hexokinase:

Enzyme which catalyses first regulatory step of glycolysis and is inhibited by Fructose-6-phosphate. So when PFK is inhibited Fructose-6-phosphate and glucose-6-phosphate builds up and hence it can inhibit hexokinase.

Pyruvate kinase:

Enzyme catalysis the third Irreversible step of glycolysis. it is activated by the high concentration of Fructose-1,6-bisphosphate and the ATP will allosterically inhibit the enzyme.